Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the major yellow pigment of turmeric, a commonly used spice, derived from the rhizome of the herb Curcuma longa Linn. In the Indian subcontinent and Southeast Asia, turmeric has traditionally been used as a treatment for inflammation, skin wounds, and tumors. In preclinical animal models, curcumin has shown cancer chemo preventive, antineoplastic and anti-inflammatory properties (Kelloff, G. I., et al, J. Cell Biochem., 1996, 265:54-71). Especially interesting is its ability to prevent the formation of carcinogen-induced intestinal premalignant lesions and malignancies in rats (Rao, C. V. et al, Cancer Res., 1995, 55:259-66; Kawamori, T. et al, Cancer Res., 1999, 59:597-601), and in the multiple neoplasia mouse (Mahmood, N. N. et al, Carcinogenesis, 2000, 31:921-27), a genetic model of the human disease familial adenomatous polyposis. Curcumin acts as a scavenger of oxygen species such as hydroxyl radical, superoxide anion and singlet oxygen (Subramanian, M. et al, Mutat. Res., 1994, 311:249-55; Tonnesen, H. H. et al, Int. J. Pharm., 1992, 87:79-87; Reddy, A. C. P. et al, Mol. Cell. Biochem., 1994, 137:1-8) and interferes with lipid peroxidation (Donatus, I. A., Biochem. Pharmacol., 1990, 39:1869-75; Sharma, S. C. et al, Biochem. Pharmacol., 1972, 21:1210-14).
Curcumin suppresses a number of key elements in cellular signal induction pathways pertinent to growth, differentiation and malignant transformations. Among signaling events inhibited by curcumin are protein kinases (Liu, J. V. et al, Carcinogenesis, 1993, 14:857-61), c-Jun/AP-1 activation (Huang, T. S. et al, Proc. Natl. Acad. Sci., 1991, 88:5292-96), prostaglandin biosynthesis (Huang, M-T. et al, In L. W. Battenberg (ed.) Cancer Chemo prevention, CRC Press, Boca Raton, 1992, pp 375-91) and activity and expression of the enzyme cyclooxygenase-2 (Huang, M. T., et al, Cancer Res., 1991, 51:813-19; Zhang, F. et al, Carcinogenesis, 1999, 20:445-51). This latter property is probably mediated by the ability of curcumin to block activation of the transcription factor NF-κB at the level of the NF-κB inducing kinase/IKKα/β signalling complex (Plummer, S. et al, Oncogene, 1999, 18:6013-20).
Despite this impressive array of beneficial bioactivities, the bioavailability of curcumin in animals and man remains low. In rodents, curcumin demonstrates poor systemic bioavailability (Ireson, C. R. et al, Cancer Res., 2001, 41:1058-64) which may be related to its inadequate absorption and fast metabolism. Curcumin bioavailability may also be poor in humans as seen from the results of a pilot study of a standardized turmeric extract in colorectal cancer patients (Sharma, R. A. et al, Clin. Cancer Res., 2001, 7:1834-1900).
Bioavailable curcumin formulation is a composition containing curcuminoid mixture and an added essential oil of turmeric, wherein the essential oil is present in an amount sufficient to cause an enhancement of bioavailability of the curcumin. The essential oil of turmeric contains turmerones principally α-turmerone and ar-turmerone. In earlier clinical trial Bioavailable curcumin formulation has shown higher bioavailability when compared with turmeric extract containing 95% total curcuminoids. Moreover, the curcumin was detected up to 8 hours in the blood of subjects administered with Bioavailable curcumin formulation as compared to only 4.5 hours in the subjects administered with turmeric extract containing 95% curcuminoids (Antony et al., Indian J Pharm Sci. 2008; 70:445-449). In a recent study by Yue et al., the effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein activities and mRNA expression were also evaluated. The authors concluded that the transport of curcumin in Caco-2 cell monolayers could be enhanced in the presence of turmerones. This study further validated our findings with Bioavailable curcumin formulation (Yue, G. L. et al, J Med Food, 2012, 15:242-252).
Controlled drug delivery systems deliver drug to the body so as to establish therapeutically effective blood levels of the active ingredient and once these blood levels are achieved they continue to maintain constant blood levels for long durations by delivering the drug to the body at the same rate as the body eliminates the drug. By avoiding peaks and troughs in blood levels associated with conventional dosage forms, controlled drug delivery systems lower the incidence of adverse effects or side effects. Very importantly controlled drug delivery systems reduce the frequency of dosing leading to convenience to the patient in terms of dosing and compliance to specified dosage regimens.
The convenience of administering a single dose of a medication which releases active ingredients over an extended period of time as opposed to the administration of a number of single doses at regular intervals has long been recognized in the pharmaceutical arts. The advantage to the patient and clinician in having consistent and blood levels of medication over an extended period of time are likewise recognized.
It is generally known that the rate at which an oral controlled drug delivery system delivers the drug into the blood is not the same as the rate at which it releases the drug into a test aqueous fluid because the gastrointestinal fluid's pH, composition and agitation intensity change with the specific location of the drug delivery system in the gastrointestinal tract i.e. from the stomach to the colon, fasted versus fed state, type and amount of food ingested, and also vary from individual to individual. In addition, the drug may not be absorbed in the same manner and propensity as we move from the stomach to the colon. Some drugs have an “absorption window” i.e. they are absorbed only from the upper parts of the gastrointestinal tract, whereas there are others whose absorption from the colon is not uniform or complete.
Ethylcellulose has become a polymer widely used in pharmaceutical film coating, especially when it is necessary to produce a modified-release dosage form. Ethylcellulose is a cellulose ether made by the reaction of ethyl chloride with alkali cellulose, as expressed by the reaction: RONa+C2H5CI→ROC2H5+NaCI, where R represents the cellulose radical. The structure that is most widely accepted for the cellulose molecule is a chain of β anhydroglucose units joined together by acetal linkages. These long, oxygen-linked anhydroglucose-unit chains have great strength, which is passed on to cellulose derivatives such as nitrocellulose, cellulose acetate, and ethylcellulose. The properties of flexibility and toughness in these derivatives are directly attributable to this long-chain structure.
Ethylcellulose is practically colorless, and retains this condition under a wide range of uses. Ethylcellulose is compatible with an unusually wide range of resins and plasticizers, including oils and waxes. It is soluble in a wide variety of solvents, thus making it easy to formulate this versatile material for any purpose where solvent application is desirable. Useful solvents among them are the esters, aromatic hydrocarbons, alcohols, ketones, and chlorinated solvents.
Shellac is a well-known commercial resin which originates as a secretion of an insect, Laccifer lacca or Tachardia lacca, found in Eastern countries, such as India, Pakistan and Sri Lanka. Principal components of shellac include aleuritic acid, shellolic acid and jalaric acid. Under some conditions, shellac can polymerize. However, shellac is not generally considered to be a polymer.
Shellac has been used as a coating on some foods and medications in order to improve their appearance. Examples of foods on which shellac has been applied include apples and confections. Forms of medications on which shellac has been employed as a coating include pills and tablets.
Although shellac coatings are enteric and non-toxic, shellac exhibits physical properties which make formation of such coatings problematic. For example, shellac is not water-soluble and has a melting point in the range of between about 75-80° C. Therefore, in order to minimize damage to surfaces to which it is applied, shellac typically must be dissolved in a medium before it is applied to a surface. The solvent can then be evaporated to leave a shellac coating.
Others have provided technologies for coating of tablets, pills, pellets etc using various polymers to protect the active drug in the stomach environment and to release the medicament in the intestine.